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01-08-2018 | Original Article

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

Authors: Gregory James, Kathleen A. Sluka, Linda Blomster, Leanne Hall, Annina B. Schmid, Cindy C. Shu, Christopher B. Little, James Melrose, Paul W. Hodges

Published in: European Spine Journal | Issue 8/2018

Abstract

Purpose

Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle.

Methods

Anterolateral lesions were induced at L3–4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals.

Results

A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased.

Conclusions

These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Available only for authorised users

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Title: Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury
Authors: Gregory James
Kathleen A. Sluka
Linda Blomster
Leanne Hall
Annina B. Schmid
Cindy C. Shu
Christopher B. Little
James Melrose
Paul W. Hodges
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 8/2018
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-018-5652-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

Abstract

Purpose

Methods

Results

Conclusions

Graphical abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Graphical abstract

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